Abstract

The visualization of optical phase can provide abundant information when imaging transparent specimen. We present a novel phase sensitive imaging design capable of obtaining phase contours of transparent biological cells through laser oblique scanning optical microscope (LOSOM). LOSOM is based on the introduction of a fluorescent medium behind the specimen to generate a differential phase-sensitive image, thus, the complicated phase retardation alignment procedure associated with differential interference contrast (DIC) microscopy can be eliminated. Moreover, multi-modality fluorescence and phase relief imaging can be attained in a single system with fluorescently labeled specimens.

© 2012 OSA

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2012 (2)

T. Peng, H. Xie, Y. Ding, W. Wang, Z. Li, D. Jin, Y. Tang, Q. Ren, and P. Xi, “CRAFT: Multimodality confocal skin imaging for early cancer diagnosis,” J Biophotonics 5(5-6), 469–476 (2012).
[CrossRef] [PubMed]

T. N. Ford, D. Lim, and J. Mertz, “Fast optically sectioned fluorescence HiLo endomicroscopy,” J. Biomed. Opt. 17(2), 021105 (2012).
[CrossRef] [PubMed]

2009 (1)

2008 (1)

A. Sakaue-Sawano, H. Kurokawa, T. Morimura, A. Hanyu, H. Hama, H. Osawa, S. Kashiwagi, K. Fukami, T. Miyata, H. Miyoshi, T. Imamura, M. Ogawa, H. Masai, and A. Miyawaki, “Visualizing spatiotemporal dynamics of multicellular cell-cycle progression,” Cell 132(3), 487–498 (2008).
[CrossRef] [PubMed]

2006 (1)

2005 (3)

2004 (1)

H. Hama, C. Hara, K. Yamaguchi, and A. Miyawaki, “PKC signaling mediates global enhancement of excitatory synaptogenesis in neurons triggered by local contact with astrocytes,” Neuron 41(3), 405–415 (2004).
[CrossRef] [PubMed]

2003 (1)

W. B. Amos, S. Reichelt, D. M. Cattermole, and J. Laufer, “Re-evaluation of differential phase contrast (DPC) in a scanning laser microscope using a split detector as an alternative to differential interference contrast (DIC) optics,” J. Microsc. 210(2), 166–175 (2003).
[CrossRef] [PubMed]

2002 (1)

E. D. Barone-Nugent, A. Barty, and K. A. Nugent, “Quantitative phase-amplitude microscopy I: optical microscopy,” J. Microsc. 206(3), 194–203 (2002).
[CrossRef] [PubMed]

2001 (1)

I. Maeda, Y. Kohara, M. Yamamoto, and A. Sugimoto, “Large-scale analysis of gene function in Caenorhabditis elegans by high-throughput RNAi,” Curr. Biol. 11(3), 171–176 (2001).
[CrossRef] [PubMed]

1999 (2)

1993 (1)

H. Gundlach, “Phase contrast and differential interference contrast instrumentation and applications in cell, developmental, and marine biology,” Opt. Eng. 32(12), 3223–3228 (1993).
[CrossRef]

1992 (1)

C. J. Cogswell and C. J. R. Sheppard, “Confocal differential interference contrast (DIC) microscopy: including a theoretical analysis of conventional and confocal DIC imaging,” J. Microsc. 165(1), 81–101 (1992).
[CrossRef]

1991 (1)

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, and C. A. Puliafito, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

1985 (1)

B. Kachar, “Asymmetric illumination contrast: a method of image formation for video light microscopy,” Science 227(4688), 766–768 (1985).
[CrossRef] [PubMed]

1977 (1)

R. Hoffman, “The modulation contrast microscope: principles and performance,” J. Microsc. 110(3), 205–222 (1977).
[CrossRef]

1955 (1)

G. Nomarski, “Differential microinterferometer with polarized waves,” J. Phys. Radium 16, 9S–11S (1955).

1942 (2)

F. Zernike, “Phase contrast, a new method for the microscopic observation of transparent objects,” Physica 9(7), 686–698 (1942).
[CrossRef]

F. Zernike, “Phase contrast, a new method for the microscopic observation of transparent objects part II,” Physica 9(10), 974–986 (1942).
[CrossRef]

Amos, W. B.

W. B. Amos, S. Reichelt, D. M. Cattermole, and J. Laufer, “Re-evaluation of differential phase contrast (DPC) in a scanning laser microscope using a split detector as an alternative to differential interference contrast (DIC) optics,” J. Microsc. 210(2), 166–175 (2003).
[CrossRef] [PubMed]

Barone-Nugent, E. D.

E. D. Barone-Nugent, A. Barty, and K. A. Nugent, “Quantitative phase-amplitude microscopy I: optical microscopy,” J. Microsc. 206(3), 194–203 (2002).
[CrossRef] [PubMed]

Barty, A.

E. D. Barone-Nugent, A. Barty, and K. A. Nugent, “Quantitative phase-amplitude microscopy I: optical microscopy,” J. Microsc. 206(3), 194–203 (2002).
[CrossRef] [PubMed]

Cattermole, D. M.

W. B. Amos, S. Reichelt, D. M. Cattermole, and J. Laufer, “Re-evaluation of differential phase contrast (DPC) in a scanning laser microscope using a split detector as an alternative to differential interference contrast (DIC) optics,” J. Microsc. 210(2), 166–175 (2003).
[CrossRef] [PubMed]

Chang, W.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, and C. A. Puliafito, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

Chu, K. K.

Cody, S. H.

S. H. Cody, S. D. Xiang, M. J. Layton, E. Handman, M. H. C. Lam, J. E. Layton, E. C. Nice, and J. K. Heath, “A simple method allowing DIC imaging in conjunction with confocal microscopy,” J. Microsc. 217(3), 265–274 (2005).
[CrossRef] [PubMed]

Cogswell, C. J.

C. J. Cogswell and C. J. R. Sheppard, “Confocal differential interference contrast (DIC) microscopy: including a theoretical analysis of conventional and confocal DIC imaging,” J. Microsc. 165(1), 81–101 (1992).
[CrossRef]

Colomb, T.

Conchello, J. A.

Cuche, E.

Dasari, R. R.

Depeursinge, C.

Ding, Y.

T. Peng, H. Xie, Y. Ding, W. Wang, Z. Li, D. Jin, Y. Tang, Q. Ren, and P. Xi, “CRAFT: Multimodality confocal skin imaging for early cancer diagnosis,” J Biophotonics 5(5-6), 469–476 (2012).
[CrossRef] [PubMed]

Emery, Y.

Feld, M. S.

Flotte, T.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, and C. A. Puliafito, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

Ford, T. N.

T. N. Ford, D. Lim, and J. Mertz, “Fast optically sectioned fluorescence HiLo endomicroscopy,” J. Biomed. Opt. 17(2), 021105 (2012).
[CrossRef] [PubMed]

Fukami, K.

A. Sakaue-Sawano, H. Kurokawa, T. Morimura, A. Hanyu, H. Hama, H. Osawa, S. Kashiwagi, K. Fukami, T. Miyata, H. Miyoshi, T. Imamura, M. Ogawa, H. Masai, and A. Miyawaki, “Visualizing spatiotemporal dynamics of multicellular cell-cycle progression,” Cell 132(3), 487–498 (2008).
[CrossRef] [PubMed]

Gregory, K.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, and C. A. Puliafito, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

Gundlach, H.

H. Gundlach, “Phase contrast and differential interference contrast instrumentation and applications in cell, developmental, and marine biology,” Opt. Eng. 32(12), 3223–3228 (1993).
[CrossRef]

Hama, H.

A. Sakaue-Sawano, H. Kurokawa, T. Morimura, A. Hanyu, H. Hama, H. Osawa, S. Kashiwagi, K. Fukami, T. Miyata, H. Miyoshi, T. Imamura, M. Ogawa, H. Masai, and A. Miyawaki, “Visualizing spatiotemporal dynamics of multicellular cell-cycle progression,” Cell 132(3), 487–498 (2008).
[CrossRef] [PubMed]

H. Hama, C. Hara, K. Yamaguchi, and A. Miyawaki, “PKC signaling mediates global enhancement of excitatory synaptogenesis in neurons triggered by local contact with astrocytes,” Neuron 41(3), 405–415 (2004).
[CrossRef] [PubMed]

Handman, E.

S. H. Cody, S. D. Xiang, M. J. Layton, E. Handman, M. H. C. Lam, J. E. Layton, E. C. Nice, and J. K. Heath, “A simple method allowing DIC imaging in conjunction with confocal microscopy,” J. Microsc. 217(3), 265–274 (2005).
[CrossRef] [PubMed]

Hanyu, A.

A. Sakaue-Sawano, H. Kurokawa, T. Morimura, A. Hanyu, H. Hama, H. Osawa, S. Kashiwagi, K. Fukami, T. Miyata, H. Miyoshi, T. Imamura, M. Ogawa, H. Masai, and A. Miyawaki, “Visualizing spatiotemporal dynamics of multicellular cell-cycle progression,” Cell 132(3), 487–498 (2008).
[CrossRef] [PubMed]

Hara, C.

H. Hama, C. Hara, K. Yamaguchi, and A. Miyawaki, “PKC signaling mediates global enhancement of excitatory synaptogenesis in neurons triggered by local contact with astrocytes,” Neuron 41(3), 405–415 (2004).
[CrossRef] [PubMed]

Heath, J. K.

S. H. Cody, S. D. Xiang, M. J. Layton, E. Handman, M. H. C. Lam, J. E. Layton, E. C. Nice, and J. K. Heath, “A simple method allowing DIC imaging in conjunction with confocal microscopy,” J. Microsc. 217(3), 265–274 (2005).
[CrossRef] [PubMed]

Hee, M. R.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, and C. A. Puliafito, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

Hoffman, R.

R. Hoffman, “The modulation contrast microscope: principles and performance,” J. Microsc. 110(3), 205–222 (1977).
[CrossRef]

Huang, D.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, and C. A. Puliafito, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

Ikeda, T.

Imamura, T.

A. Sakaue-Sawano, H. Kurokawa, T. Morimura, A. Hanyu, H. Hama, H. Osawa, S. Kashiwagi, K. Fukami, T. Miyata, H. Miyoshi, T. Imamura, M. Ogawa, H. Masai, and A. Miyawaki, “Visualizing spatiotemporal dynamics of multicellular cell-cycle progression,” Cell 132(3), 487–498 (2008).
[CrossRef] [PubMed]

Jin, D.

T. Peng, H. Xie, Y. Ding, W. Wang, Z. Li, D. Jin, Y. Tang, Q. Ren, and P. Xi, “CRAFT: Multimodality confocal skin imaging for early cancer diagnosis,” J Biophotonics 5(5-6), 469–476 (2012).
[CrossRef] [PubMed]

Kachar, B.

B. Kachar, “Asymmetric illumination contrast: a method of image formation for video light microscopy,” Science 227(4688), 766–768 (1985).
[CrossRef] [PubMed]

Kashiwagi, S.

A. Sakaue-Sawano, H. Kurokawa, T. Morimura, A. Hanyu, H. Hama, H. Osawa, S. Kashiwagi, K. Fukami, T. Miyata, H. Miyoshi, T. Imamura, M. Ogawa, H. Masai, and A. Miyawaki, “Visualizing spatiotemporal dynamics of multicellular cell-cycle progression,” Cell 132(3), 487–498 (2008).
[CrossRef] [PubMed]

Kohara, Y.

I. Maeda, Y. Kohara, M. Yamamoto, and A. Sugimoto, “Large-scale analysis of gene function in Caenorhabditis elegans by high-throughput RNAi,” Curr. Biol. 11(3), 171–176 (2001).
[CrossRef] [PubMed]

Kurokawa, H.

A. Sakaue-Sawano, H. Kurokawa, T. Morimura, A. Hanyu, H. Hama, H. Osawa, S. Kashiwagi, K. Fukami, T. Miyata, H. Miyoshi, T. Imamura, M. Ogawa, H. Masai, and A. Miyawaki, “Visualizing spatiotemporal dynamics of multicellular cell-cycle progression,” Cell 132(3), 487–498 (2008).
[CrossRef] [PubMed]

Lam, M. H. C.

S. H. Cody, S. D. Xiang, M. J. Layton, E. Handman, M. H. C. Lam, J. E. Layton, E. C. Nice, and J. K. Heath, “A simple method allowing DIC imaging in conjunction with confocal microscopy,” J. Microsc. 217(3), 265–274 (2005).
[CrossRef] [PubMed]

Laufer, J.

W. B. Amos, S. Reichelt, D. M. Cattermole, and J. Laufer, “Re-evaluation of differential phase contrast (DPC) in a scanning laser microscope using a split detector as an alternative to differential interference contrast (DIC) optics,” J. Microsc. 210(2), 166–175 (2003).
[CrossRef] [PubMed]

Layton, J. E.

S. H. Cody, S. D. Xiang, M. J. Layton, E. Handman, M. H. C. Lam, J. E. Layton, E. C. Nice, and J. K. Heath, “A simple method allowing DIC imaging in conjunction with confocal microscopy,” J. Microsc. 217(3), 265–274 (2005).
[CrossRef] [PubMed]

Layton, M. J.

S. H. Cody, S. D. Xiang, M. J. Layton, E. Handman, M. H. C. Lam, J. E. Layton, E. C. Nice, and J. K. Heath, “A simple method allowing DIC imaging in conjunction with confocal microscopy,” J. Microsc. 217(3), 265–274 (2005).
[CrossRef] [PubMed]

Li, Z.

T. Peng, H. Xie, Y. Ding, W. Wang, Z. Li, D. Jin, Y. Tang, Q. Ren, and P. Xi, “CRAFT: Multimodality confocal skin imaging for early cancer diagnosis,” J Biophotonics 5(5-6), 469–476 (2012).
[CrossRef] [PubMed]

Lim, D.

T. N. Ford, D. Lim, and J. Mertz, “Fast optically sectioned fluorescence HiLo endomicroscopy,” J. Biomed. Opt. 17(2), 021105 (2012).
[CrossRef] [PubMed]

Lin, C. P.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, and C. A. Puliafito, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

Maeda, I.

I. Maeda, Y. Kohara, M. Yamamoto, and A. Sugimoto, “Large-scale analysis of gene function in Caenorhabditis elegans by high-throughput RNAi,” Curr. Biol. 11(3), 171–176 (2001).
[CrossRef] [PubMed]

Magistretti, P. J.

Marquet, P.

Masai, H.

A. Sakaue-Sawano, H. Kurokawa, T. Morimura, A. Hanyu, H. Hama, H. Osawa, S. Kashiwagi, K. Fukami, T. Miyata, H. Miyoshi, T. Imamura, M. Ogawa, H. Masai, and A. Miyawaki, “Visualizing spatiotemporal dynamics of multicellular cell-cycle progression,” Cell 132(3), 487–498 (2008).
[CrossRef] [PubMed]

Mehta, S. B.

Mertz, J.

T. N. Ford, D. Lim, and J. Mertz, “Fast optically sectioned fluorescence HiLo endomicroscopy,” J. Biomed. Opt. 17(2), 021105 (2012).
[CrossRef] [PubMed]

R. Yi, K. K. Chu, and J. Mertz, “Graded-field microscopy with white light,” Opt. Express 14(12), 5191–5200 (2006).
[CrossRef] [PubMed]

Miyata, T.

A. Sakaue-Sawano, H. Kurokawa, T. Morimura, A. Hanyu, H. Hama, H. Osawa, S. Kashiwagi, K. Fukami, T. Miyata, H. Miyoshi, T. Imamura, M. Ogawa, H. Masai, and A. Miyawaki, “Visualizing spatiotemporal dynamics of multicellular cell-cycle progression,” Cell 132(3), 487–498 (2008).
[CrossRef] [PubMed]

Miyawaki, A.

A. Sakaue-Sawano, H. Kurokawa, T. Morimura, A. Hanyu, H. Hama, H. Osawa, S. Kashiwagi, K. Fukami, T. Miyata, H. Miyoshi, T. Imamura, M. Ogawa, H. Masai, and A. Miyawaki, “Visualizing spatiotemporal dynamics of multicellular cell-cycle progression,” Cell 132(3), 487–498 (2008).
[CrossRef] [PubMed]

H. Hama, C. Hara, K. Yamaguchi, and A. Miyawaki, “PKC signaling mediates global enhancement of excitatory synaptogenesis in neurons triggered by local contact with astrocytes,” Neuron 41(3), 405–415 (2004).
[CrossRef] [PubMed]

Miyoshi, H.

A. Sakaue-Sawano, H. Kurokawa, T. Morimura, A. Hanyu, H. Hama, H. Osawa, S. Kashiwagi, K. Fukami, T. Miyata, H. Miyoshi, T. Imamura, M. Ogawa, H. Masai, and A. Miyawaki, “Visualizing spatiotemporal dynamics of multicellular cell-cycle progression,” Cell 132(3), 487–498 (2008).
[CrossRef] [PubMed]

Morimura, T.

A. Sakaue-Sawano, H. Kurokawa, T. Morimura, A. Hanyu, H. Hama, H. Osawa, S. Kashiwagi, K. Fukami, T. Miyata, H. Miyoshi, T. Imamura, M. Ogawa, H. Masai, and A. Miyawaki, “Visualizing spatiotemporal dynamics of multicellular cell-cycle progression,” Cell 132(3), 487–498 (2008).
[CrossRef] [PubMed]

Nice, E. C.

S. H. Cody, S. D. Xiang, M. J. Layton, E. Handman, M. H. C. Lam, J. E. Layton, E. C. Nice, and J. K. Heath, “A simple method allowing DIC imaging in conjunction with confocal microscopy,” J. Microsc. 217(3), 265–274 (2005).
[CrossRef] [PubMed]

Nomarski, G.

G. Nomarski, “Differential microinterferometer with polarized waves,” J. Phys. Radium 16, 9S–11S (1955).

Nugent, K. A.

E. D. Barone-Nugent, A. Barty, and K. A. Nugent, “Quantitative phase-amplitude microscopy I: optical microscopy,” J. Microsc. 206(3), 194–203 (2002).
[CrossRef] [PubMed]

Ogawa, M.

A. Sakaue-Sawano, H. Kurokawa, T. Morimura, A. Hanyu, H. Hama, H. Osawa, S. Kashiwagi, K. Fukami, T. Miyata, H. Miyoshi, T. Imamura, M. Ogawa, H. Masai, and A. Miyawaki, “Visualizing spatiotemporal dynamics of multicellular cell-cycle progression,” Cell 132(3), 487–498 (2008).
[CrossRef] [PubMed]

Osawa, H.

A. Sakaue-Sawano, H. Kurokawa, T. Morimura, A. Hanyu, H. Hama, H. Osawa, S. Kashiwagi, K. Fukami, T. Miyata, H. Miyoshi, T. Imamura, M. Ogawa, H. Masai, and A. Miyawaki, “Visualizing spatiotemporal dynamics of multicellular cell-cycle progression,” Cell 132(3), 487–498 (2008).
[CrossRef] [PubMed]

Peng, T.

T. Peng, H. Xie, Y. Ding, W. Wang, Z. Li, D. Jin, Y. Tang, Q. Ren, and P. Xi, “CRAFT: Multimodality confocal skin imaging for early cancer diagnosis,” J Biophotonics 5(5-6), 469–476 (2012).
[CrossRef] [PubMed]

Popescu, G.

Preza, C.

Puliafito, C. A.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, and C. A. Puliafito, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

Rappaz, B.

Reichelt, S.

W. B. Amos, S. Reichelt, D. M. Cattermole, and J. Laufer, “Re-evaluation of differential phase contrast (DPC) in a scanning laser microscope using a split detector as an alternative to differential interference contrast (DIC) optics,” J. Microsc. 210(2), 166–175 (2003).
[CrossRef] [PubMed]

Ren, Q.

T. Peng, H. Xie, Y. Ding, W. Wang, Z. Li, D. Jin, Y. Tang, Q. Ren, and P. Xi, “CRAFT: Multimodality confocal skin imaging for early cancer diagnosis,” J Biophotonics 5(5-6), 469–476 (2012).
[CrossRef] [PubMed]

Sakaue-Sawano, A.

A. Sakaue-Sawano, H. Kurokawa, T. Morimura, A. Hanyu, H. Hama, H. Osawa, S. Kashiwagi, K. Fukami, T. Miyata, H. Miyoshi, T. Imamura, M. Ogawa, H. Masai, and A. Miyawaki, “Visualizing spatiotemporal dynamics of multicellular cell-cycle progression,” Cell 132(3), 487–498 (2008).
[CrossRef] [PubMed]

Schuman, J. S.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, and C. A. Puliafito, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

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S. B. Mehta and C. J. R. Sheppard, “Quantitative phase-gradient imaging at high resolution with asymmetric illumination-based differential phase contrast,” Opt. Lett. 34(13), 1924–1926 (2009).
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[CrossRef]

Snyder, D. L.

Stinson, W. G.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, and C. A. Puliafito, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

Sugimoto, A.

I. Maeda, Y. Kohara, M. Yamamoto, and A. Sugimoto, “Large-scale analysis of gene function in Caenorhabditis elegans by high-throughput RNAi,” Curr. Biol. 11(3), 171–176 (2001).
[CrossRef] [PubMed]

Swanson, E. A.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, and C. A. Puliafito, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

Tang, Y.

T. Peng, H. Xie, Y. Ding, W. Wang, Z. Li, D. Jin, Y. Tang, Q. Ren, and P. Xi, “CRAFT: Multimodality confocal skin imaging for early cancer diagnosis,” J Biophotonics 5(5-6), 469–476 (2012).
[CrossRef] [PubMed]

Wang, W.

T. Peng, H. Xie, Y. Ding, W. Wang, Z. Li, D. Jin, Y. Tang, Q. Ren, and P. Xi, “CRAFT: Multimodality confocal skin imaging for early cancer diagnosis,” J Biophotonics 5(5-6), 469–476 (2012).
[CrossRef] [PubMed]

Xi, P.

T. Peng, H. Xie, Y. Ding, W. Wang, Z. Li, D. Jin, Y. Tang, Q. Ren, and P. Xi, “CRAFT: Multimodality confocal skin imaging for early cancer diagnosis,” J Biophotonics 5(5-6), 469–476 (2012).
[CrossRef] [PubMed]

Xiang, S. D.

S. H. Cody, S. D. Xiang, M. J. Layton, E. Handman, M. H. C. Lam, J. E. Layton, E. C. Nice, and J. K. Heath, “A simple method allowing DIC imaging in conjunction with confocal microscopy,” J. Microsc. 217(3), 265–274 (2005).
[CrossRef] [PubMed]

Xie, H.

T. Peng, H. Xie, Y. Ding, W. Wang, Z. Li, D. Jin, Y. Tang, Q. Ren, and P. Xi, “CRAFT: Multimodality confocal skin imaging for early cancer diagnosis,” J Biophotonics 5(5-6), 469–476 (2012).
[CrossRef] [PubMed]

Yamaguchi, K.

H. Hama, C. Hara, K. Yamaguchi, and A. Miyawaki, “PKC signaling mediates global enhancement of excitatory synaptogenesis in neurons triggered by local contact with astrocytes,” Neuron 41(3), 405–415 (2004).
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Yamamoto, M.

I. Maeda, Y. Kohara, M. Yamamoto, and A. Sugimoto, “Large-scale analysis of gene function in Caenorhabditis elegans by high-throughput RNAi,” Curr. Biol. 11(3), 171–176 (2001).
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F. Zernike, “Phase contrast, a new method for the microscopic observation of transparent objects part II,” Physica 9(10), 974–986 (1942).
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Appl. Opt. (1)

Cell (1)

A. Sakaue-Sawano, H. Kurokawa, T. Morimura, A. Hanyu, H. Hama, H. Osawa, S. Kashiwagi, K. Fukami, T. Miyata, H. Miyoshi, T. Imamura, M. Ogawa, H. Masai, and A. Miyawaki, “Visualizing spatiotemporal dynamics of multicellular cell-cycle progression,” Cell 132(3), 487–498 (2008).
[CrossRef] [PubMed]

Curr. Biol. (1)

I. Maeda, Y. Kohara, M. Yamamoto, and A. Sugimoto, “Large-scale analysis of gene function in Caenorhabditis elegans by high-throughput RNAi,” Curr. Biol. 11(3), 171–176 (2001).
[CrossRef] [PubMed]

J Biophotonics (1)

T. Peng, H. Xie, Y. Ding, W. Wang, Z. Li, D. Jin, Y. Tang, Q. Ren, and P. Xi, “CRAFT: Multimodality confocal skin imaging for early cancer diagnosis,” J Biophotonics 5(5-6), 469–476 (2012).
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T. N. Ford, D. Lim, and J. Mertz, “Fast optically sectioned fluorescence HiLo endomicroscopy,” J. Biomed. Opt. 17(2), 021105 (2012).
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[CrossRef] [PubMed]

C. J. Cogswell and C. J. R. Sheppard, “Confocal differential interference contrast (DIC) microscopy: including a theoretical analysis of conventional and confocal DIC imaging,” J. Microsc. 165(1), 81–101 (1992).
[CrossRef]

S. H. Cody, S. D. Xiang, M. J. Layton, E. Handman, M. H. C. Lam, J. E. Layton, E. C. Nice, and J. K. Heath, “A simple method allowing DIC imaging in conjunction with confocal microscopy,” J. Microsc. 217(3), 265–274 (2005).
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H. Hama, C. Hara, K. Yamaguchi, and A. Miyawaki, “PKC signaling mediates global enhancement of excitatory synaptogenesis in neurons triggered by local contact with astrocytes,” Neuron 41(3), 405–415 (2004).
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[CrossRef]

F. Zernike, “Phase contrast, a new method for the microscopic observation of transparent objects part II,” Physica 9(10), 974–986 (1942).
[CrossRef]

Science (2)

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, and C. A. Puliafito, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
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Figures (5)

Fig. 1
Fig. 1

(a) Simplified schematic diagram of the LOSOM system. The incident beam and the dichroic of the confocal system are not illustrated. The red beam represents the axial beam pathway of a confocal microscope, and the light blue beam indicates the beam pathway in the LOSOM. (b) Geometrical relationship between a light beam diameter (red circle) and an aperture of the collecting lens (yellow circle). O and O' , are centers of the beam and the aperture, respectively; r 1 and r 2 , are radii of the beam and the aperture, respectively; D denotes the distance of |OO'| ; L denotes a common chordal length of the overlapping areas; S 1 , S 2 are the areas of the beam and aperture, respectively; θ, θ 1 , θ 2 are the angles in the presented triangle. (c) The entire LOSOM system is illustrated, highlighting the telescope composed of the scan lens and the tube lens. The galvo-scanner is tilted to provide the oblique illumination with the aid of a fluorescent medium. DC: dichroic mirror.

Fig. 2
Fig. 2

Simulation of LOSOM in response to variations in the optical path. (a) Object optical path difference (OPD), the grayscale represents the optical phase. (b)-(c) Intensity distributions of the phase relief generated using opposite directions of illumination rays. (d) OPD along the azimuth axis, corresponding to (a). (e)-(f) Amplitude profiles along the azimuth axis, corresponding to (b)-(c), respectively.

Fig. 3
Fig. 3

Comparison of images captured with DIC and LOSOM. The relief appearance of the same HeLa cells can be compared with (a) DIC (Carl Zeiss, NA = 0.4) and (b-c) LOSOM (Nikon, NA = 0.3). Scale bar: 30 μm.

Fig. 4
Fig. 4

Pseudo-color images of a mouse kidney section (F-24630, Invitrogen) using LOSOM to reveal DAPI fluorescent staining for nuclear material (a, d). Note that images of oblique fluorescent illumination show a relief-like structure in the tissue sections (b, e) and the combined images (c, f). Images (a-c) are taken with 10x, NA 0.3 objective, and (d-f) are taken with 20x, NA 0.45 objective. Scale bar: 30 μm.

Fig. 5
Fig. 5

A series of optical sections of the mouse kidney taken at 2 μm intervals using LOSOM with the 10x objective. Scale bar: 30 μm.

Equations (10)

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U(ξ,η)= X,Y u 0 ( x 1 , y 1 )exp[i k f 1 ( x 1 ξ+ y 1 η)]exp(ikz)d x 1 d y 1 ,
u 1 ( x 2 , y 2 )= Ξ,Ω U(ξ,η)exp[i k f 2 ( x 2 ξ+ y 2 η)]dξdη =exp(ikz) Ξ,Ω X,Y u 0 ( x 1 , y 1 )exp{ik[( x 1 f 1 + x 2 f 2 )ξ +( y 1 f 1 + y 2 f 2 )η]}d x 1 d y 1 dξdη,
u 1 (M x 1 ,M y 1 )= u 0 ( x 1 , y 1 )exp(ikz),
U(ξ',η')= X,Y u 0 ( x 1 , y 1 )exp{ik[ x 1 ( ξ' f 1 +ϕ)+ η' f 1 y 1 ]}exp(ikz)d x 1 d y 1 ,
circ( x 0 , y 0 ,r)={ 1, (x x 0 ) 2 + (y y 0 ) 2 r 2 0, otherwise .
I'(ξ,η,z)= 4 I 0 π a 2 circ(ϕ f 1 ,0, a 2 )circ(0,0, W 2 ).
dS dD = d S 1 dD + d S 2 dD = L 2 2 dθ dD ..
dθ dD = D r 1 r 2 sinθ = 2 L ,
dS dx = dS dD dD dx =L f 1 dρ dx .
dI dx =C dρ dx ,

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